Members of the transforming growth factor-β (TGF-β) family play key roles in embryogenesis and in maintaining tissue homeostasis, and their perturbation can result in a broad range of diseases. One way TGF-β family signaling pathways are kept in check is by reversible (de)phosphorylation of intracellular Smad effectors. In this issue of EMBO Reports, Park et al [1] identify the phosphatase wild-type p53-induced phosphatase 1 (Wip1) as a negative regulator of TGF-β family signaling. Mechanistically, Wip1 constrains TGF-β family signaling through direct dephosphorylation of Thr277, an activating MAP kinase phosphorylation site located in the linker region of the common mediator Smad4.

中文翻译：

---

使用Wip控制Smad4信令。

转化生长因子-β（TGF-β）家族的成员在胚胎发生和维持组织稳态中起着关键作用，它们的扰动可导致多种疾病。抑制TGF-β家族信号传导途径的一种方法是通过细胞内Smad效应子的可逆（去磷酸化）。在本期《 EMBO报告》中，Park等人[1]将磷酸酶野生型p53诱导的磷酸酶1（Wip1）鉴定为TGF-β家族信号转导的负调节剂。从机械上讲，Wip1通过Thr277的直接去磷酸化来限制TGF-β家族信号传导，Thr277是位于共同介体Smad4的连接子区域的活化MAP激酶磷酸化位点。